Placental Heterogeneity in Stillbirth and Its Relations to Maternal Exogenous Characteristics.

INTRODUCTION: Heterogeneous patterns of placental lesions in stillbirth signal important variations in placental histopathology that may be diagnostic in stillbirth. We explore placental heterogeneity and its associations with maternal characteristics (including HIV) using latent class analysis. METHODS: Placental and maternal data and slides were assessed retrospectively for 122 confirmed stillbirths (gestational age ≥ 28 weeks) delivered at a major South African academic hospital between January 2016-July 2018. The slides were reviewed by 2 pathologists and classified using the Amsterdam Consensus Classification System. Latent class analyses were conducted on raw data. RESULTS: We identify 5 latent placental classes in stillbirth based on similarity in patterns of observed diagnostic criteria and their associations with maternal characteristics. Three classes bear similarity to generalized patterns of placental injury identified previously. Our study shows that intrauterine infection was the commonest histopathological condition associated with stillbirth in our setting. Novel findings include 2 classes, distinguished by high placental RPH and maternal HIV, respectively, and the non-emergence of a class distinguished by VUE. CONCLUSION: The size and content of the latent classes and their similarity/dissimilarity to the more generalized patterns identified previously suggest potential new avenues for investigation and theory development concerning the role of the placenta in stillbirth and the impact of HIV.

Diagnosing mycobacterial lymphadenitis in children using fine needle aspiration biopsy: cytomorphology, ZN staining and autofluorescence -- making more of less.

Although the incidence of TB has stabilized or declined in most world regions, it is increasing in Africa, Southeast Asia, and the Eastern Mediterranean, fuelled by the HIV pandemic. More than 4,000 people died daily from TB-related illnesses in 2005. TB is a major cause of childhood morbidity and mortality in these developing countries, and there is an urgent need for rapid and definitive modalities for mycobacterial diagnosis in children. This prospective study in Tygerberg Hospital, Cape Town, South Africa, evaluates the ability of fine needle aspiration biopsy (FNAB) to diagnose mycobacterial lymphadenitis in children, using cytomorphology, autofluorescence on Papanicolaou stained smears, Ziehl-Nielsen (ZN) staining and/or culture. FNABs were performed on 200 children, and 25 (12.5%) aspirates were inadequate. Cultures were positive in 79/175 (45%); Mycobacterium tuberculosis was identified in 61 and Mycobacterium bovis BCG in 18 cases. Using culture as the gold standard, the concordance of the different techniques was as follows: cytomorphology 70%, ZN staining 73%, and autofluorescence 68%. Using an alternative gold standard (culture positive and/or suggestive cytomorphology plus positive autofluorescence or ZN smear), the "true" diagnostic performance of the various techniques was as follows: cytomorphology-sensitivity 78%, specificity 91%, positive predictive value (PPV) 93%, ZN staining - sensitivity 62%%, specificity 97%, PPV 97%; autofluorescence-sensitivity 67%, specificity 97%, PPV 97%; and culture-sensitivity 75%, specificity 100%, and PPV 100%. FNAB was shown to provide a rapid and definitive diagnosis in the majority of cases of suspected tuberculous lymphadenitis in children, based on cytomorphology and identification of the organism.

Mycobacterial autofluorescence in Papanicolaou-stained lymph node aspirates: a glimmer in the dark?

This study was undertaken to determine the value of incorporating fluorescence into cytopathological evaluation of lymph node fine-needle aspiration (FNA) specimens suspected of harboring mycobacterial species. The study population consisted of 1,044 HIV-positive and -negative patients referred for FNA to the cytopathology unit of a South African medical school located in a very high HIV prevalence region. Each aspirate was assessed on routine Papanicolaou-stained slides for morphologic characteristics of mycobacterial infection. The same glass slides were then viewed under fluorescent microscopy to determine the presence or absence of mycobacterial autofluorescence. Using multivariate analysis, results of both cytology and fluorescence were compared with mycobacterial culture as the final arbiter of the presence of organisms. In this large clinical study, compared with culture, cytomorphology showed sensitivity of 84.9%, but low specificity of only 50.9%. Fluorescence demonstrated lower sensitivity of 65.9%, but improved specificity of 73.0%. Taken together, positivity of both cytology and fluorescence improved specificity to 81.8%. Fluorescent microscopy is rapid, inexpensive, and cost-effective; neither radioactive materials nor further staining are required. It is felt that this methodology would be of diagnostic benefit if used on morphologically suspicious samples in areas with a high prevalence of HIV and mycobacterial infections. Appropriate therapy could be commenced within hours of FNA, with reduction in the current number of patients lost to follow-up while awaiting results of culture. The technique is readily extended to other FNA types such as deep organ aspirates. Autofluorescence of organisms specifically requires usage of Papanicolaou staining; the technique cannot be used in histopathologic specimens stained with hematoxylin-eosin.